Endocannabinoid system as a potential mechanism for n-3 long-chain polyunsaturated fatty acid mediated cardiovascular protection

Abstract

The presence of an active and functioning endocannabinoid (EC) system within cardiovascular tissues implies that this system has either a physiological or pathophysiological role (or both), and there is a substantial literature to support the notion that, in the main, they are protective in the setting of various CVD states. Moreover, there is an equally extensive literature to demonstrate the cardio- and vasculo-protective effects of n-3 long-chain (LC)-PUFA. It is now becoming evident that there appears to be a close relationship between dietary intervention with n-3 LC-PUFA and changes in tissue levels of EC, raising the question as to whether or not EC may, at least in part, play a role in mediating the cardio-and vasculo-protective effects of n-3 LC-PUFA. This brief review summarises the current understanding of how both EC and n-3 LC-PUFA exert their protective effects in three major cardiovascular disorders (hypertension, atherosclerosis and acute myocardial infarction) and attempts to identify the similarities and differences that may indicate common or integrated mechanisms. From the data available, it is unlikely that in hypertension EC mediate any beneficial effects of n-3 LC-PUFA, since they do not share common mechanisms of blood pressure reduction. However, inhibition of inflammation is an effect shared by EC and n-3 LC-PUFA in the setting of both atherosclerosis and myocardial reperfusion injury, while blockade of L-type Ca2+ channels is one of the possible common mechanisms for their antiarrhythmic effects. Although both EC and n-3 LC-PUFA demonstrate vasculo- and cardio-protection, the literature overwhelmingly shows that n-3 LC-PUFA decrease tissue levels of EC through formation of EC–n-3 LC-PUFA conjugates, which is counter-intuitive to an argument that EC may mediate the effects of n-3 LC-PUFA. However, the discovery that these conjugates have a greater affinity for cannabinoid receptors than the native EC provides a fascinating avenue for further research into novel approaches for the treatment and prevention of atherosclerosis and myocardial injury following ischaemia/reperfusion.